Are Diabetes and Weight-Loss Drugs a Good Match?

Millions worldwide are affected by type 2 diabetes, and recent international research, led by Adelaide University, the University of Oxford, ETH Zurich, and Stanford University, reveals that one in ten individuals may not respond to common diabetes medications.

The study uncovered genetic differences present in about ten percent of the population that could hinder the effectiveness of GLP-1 receptor drugs, such as Ozempic.

This research emphasizes the importance of personalized medicine when prescribing these popular medications, which are also employed for weight loss.

“Recent advancements in treating diabetes and obesity have been driven by widespread use of GLP-1 based therapies like Ozempic,” said lead researcher Dr. Mahesh Umapathysivam from Adelaide University’s Centre of Research Excellence: Translating Nutritional Science to Good Health.

“However, not all patients respond equally well,” he added. “Understanding why, and being able to predict who will benefit or not, will help us tailor treatments more effectively to individual patients.”

The findings, published in Genome Medicine, stem from numerous human and animal trials examining how specific gene variants in the PAM gene increase the risk of developing type 2 diabetes.

This study builds on previous research showing that the PAM gene worsens diabetes risk by reducing insulin production and altering hormone structures, including the GLP-1 hormone responsible for blood sugar regulation.

In this latest research, scientists showed that variations in the PAM gene made the enzyme less effective, leading to higher levels of natural GLP-1 but diminishing the hormone’s positive influence on blood sugar. This indicates a form of resistance to GLP-1 in individuals with these genetic traits.

Further investigation revealed that this genetic resistance impacts how the body responds to GLP-1 medications. For carriers of specific PAM gene variants, the medications’ ability to lower blood glucose was reduced by as much as 44% over six months.

Only about 11% of those with the more harmful PAM variant managed to reach recommended blood sugar levels while on these drugs, compared to roughly 25% of individuals without the mutation.

“Our study offers critical clinical evidence showing that certain gene variants make some people more prone to diabetes and less responsive to GLP-1 therapies,” said Dr. Umapathysivam. “As we identify more genetic markers predicting treatment response, we can combine this data to select the most effective medication for each patient.”

GLP-1 medications like Ozempic are typically injectable treatments that help control blood sugar by stimulating insulin production and suppressing appetite.

“Type 2 diabetes remains one of the leading causes of health complications and death worldwide. Despite the variety of available treatments, only half of all patients meet the target blood glucose levels,” noted Dr. Umapathysivam. “This underscores the need for more personalized treatment strategies to improve patient outcomes.”

The ongoing research, supported by Diabetes Australia, aims to expand these findings.

“We hope this work will pave the way for future genetic testing panels that identify the best medications for individual patients, thereby enhancing diabetes management and reducing adverse effects,” said Dr. Umapathysivam.